安罗替尼联合免疫治疗在非小细胞肺癌中的 研究进展及临床应用价值

Recent Advances and Clinical Value of Anlotinib Combined with Immunotherapy in Non-Small Cell Lung Cancer

摘要: 近年来，以PD-1/PD-L1抑制剂为代表的免疫治疗显著改善了晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)患者的生存预后。然而，临床实践中仍有相当比例的患者面临原发性或获得性耐药问题，同时存在疗效异质性明显、免疫相关不良反应管理复杂等挑战，需探索新的联合治疗策略以突破现有治疗瓶颈。抗血管生成药物与免疫检查点抑制剂的协同应用，为克服上述局限提供了新的临床思路。安罗替尼作为我国自主研发的多靶点酪氨酸激酶抑制剂，除具有经典抗血管生成作用外，还可通过诱导肿瘤血管正常化、缓解局部缺氧、增强CD8⁺T细胞浸润以及调控癌症相关成纤维细胞等间质成分，实现对免疫抑制性肿瘤微环境的多维干预。本文系统综述安罗替尼联合免疫治疗在NSCLC中的作用机制、优势人群特征及生物标志物研究进展，重点总结其在后线挽救、一线治疗、维持治疗及围手术期等不同治疗场景中的临床研究证据，并对安全性特征与个体化剂量优化策略进行讨论，以期为NSCLC精准治疗提供参考。

Abstract: In recent years, immunotherapy represented by PD-1/PD-L1 inhibitors has significantly improved the survival outcomes of patients with advanced non-small cell lung cancer (NSCLC). However, a considerable proportion of patients still develop primary or acquired resistance in clinical practice, accompanied by significant heterogeneity in treatment response and challenges in managing immune-related adverse events. Therefore, there is an urgent need to explore novel combination strategies to overcome current therapeutic limitations. The synergistic application of anti-angiogenic agents and immune checkpoint inhibitors offers a promising clinical approach to address these constraints. Anlotinib, a domestically developed multi-target tyrosine kinase inhibitor, not only possesses classical anti-angiogenic effects but also achieves multidimensional intervention of the immunosuppressive tumor microenvironment by inducing tumor vascular normalization, alleviating local hypoxia, enhancing CD8⁺ T cell infiltration, and regulating stromal components such as cancer-associated fibroblasts. This review systematically summarizes the mechanisms of action, characteristics of potentially beneficial populations, and biomarker research progress of anlotinib combined with immunotherapy in NSCLC. It focuses on clinical evidence from different treatment settings including later-line salvage therapy, first-line treatment, maintenance therapy, and perioperative treatment, and discusses safety profiles and individualized dose optimization strategies, aiming to provide references for precision treatment of NSCLC.